Human experimental exposure study on the uptake and urinary elimination of N-methyl-2-pyrrolidone (NMP) during simulated workplace conditions

Abstract

A human experimental study was carried out with 16 volunteers to examine the elimination of N-methyl-2-pyrrolidone (NMP) after exposure to the solvent under simulated workplace conditions. The NMP concentrations were 10, 40 and 80 mg/m³ for 2 × 4 h with an exposure-free interval of 30 min. Additionally, a peak exposure scenario (25 mg/m³ baseline, 160 mg/m³ peaks for 4 × 15 min, time-weighted average: 72 mg/m³) was tested. The influence of physical activity on the uptake and elimination of NMP was studied under otherwise identical exposure conditions but involving moderate workload on a bicycle ergometer (75 W for 6 × 10 min). The peak times and biological half-lives of urinary NMP and its main metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in urine were analysed as well as the interrelationships between exposure and biomarkers. All analytes showed a close correlation between their post-shift peak concentrations and airborne NMP. An exposure to the current German workplace limit value of 80 mg/m³ under resting conditions resulted in urinary peak concentrations of 2,400 μg/L NMP, 117 mg/g creatinine 5-HNMP and 32 mg/g creatinine 2-HMSI (workload conditions: 3,400 μg/L NMP, 150 mg/g creatinine 5-HNMP, 44 mg/g creatinine 2-HMSI). Moderate workload enhanced the total uptake of NMP by approximately one third. Differences between the estimated and the observed total amount of urinary metabolites point to a significant contribution of dermal absorption on the uptake of NMP. This aspect, together with the influence of physical workload, should be considered for the evaluation of a biological limit value for NMP.